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Objective: To investigate the role and clinical significance of p16 protein in Condyloma Acuminatum (CA) and its cancerization.Methods.. The expression of p16 protein was tested in 33 CA samples and 7 cancerized CA samples by immunohistochemical assays.Results: There was abnormal expression of p16 protein in CA and cancerized CA, mainly major protein expression. The p16 protein expresseed in different locations in different cases was as follows: In basal layer cells in normal cuits; in spinous layer, granular layer and stratum ceum layer cells in CA;in keratin pearl peripheral and spinous layer cells in cancerized CA.Conclusion: There was major expression of p16 protein in CA and cancerized CA, and these protein of the two groups might not naturally be the same. Our study indicated that in clinical practice, when major p16 protein expression in CA occurs, it’s risk of cancerization shoud be suspected.